Project Summary/Abstract: There is currently a technological gap in pencil beam scanning (PBS) proton therapy that is resulting in excess spillage of radiation dose outside of the intended target tissue. Existence of this gap represents an important problem because, until a technological solution is developed, patients undergoing PBS proton therapy will be exposed to unwanted radiation dose and the normal tissue complications. The long-term goal is to increase therapeutic efficacy and reduce the risk of side effects associated with PBS proton therapy. The overall objective of this project is to translate and validate a new collimator technology, called the dynamic collimation system (DCS), with an existing commercial PBS proton therapy delivery system in a clinical setting to limit the dose spillage. The DCS makes use of four independently controlled trimmer blades that are designed to move in synchrony with the scanned proton beam during PBS delivery. By intercepting the beam as it arrives at the lateral boundaries of the tumor, the dose distribution can be sharpened and dose to surrounding normal structures can be substantially reduced. Unlike other proposed solutions, the DCS can provide unique collimation for each energy layer of a PBS proton therapy treatment and a footprint small enough to allow placement near the surface of the patient. The rationale for the project is that the addition of the DCS to existing PBS equipment, at only a small fraction of the cost of a $30M+ proton therapy center, can rapidly translate to improved clinical care delivery. Guided by strong preliminary data from our in-silico treatment planning studies, development of the DCS will be carried out by pursing three specific aims: 1) Design, build, and validate a DCS prototype based on our extensive modeling, 2) Minimize the treatment time penalty associated with the DCS, and 3) Provide appropriate methodologies for centers to use the DCS. Under specific aim 1, an existing computer designed model will drive the physical construction of an integrated prototype system and the dosimetric performance will be validated against a model of the system. Under specific aim 2, a trimmer sequencing algorithm will be developed and tested that allows dynamic motion of trimmer leaves simultaneously with beam scanning. The purpose of this algorithm is to minimize the treatment time penalty associated with the DCS, with a target treatment time penalty of less than 2 minutes per treatment session. Under specific aim 3, a quality assurance and commissioning approach will be developed to facilitate safe and effective clinical use of the DCS by the radiation oncology community. The research proposed in this application is innovative because it represents a new and substantial departure from current collimation technologies with the introduction of a compact collimator with dynamic motion for shaping individual pencil beams layer-by-layer. This contribution is expected to be significant as the collimation system will decrease the dose to healthy tissue surrounding the target, leading to improved patient outcomes. Ultimately, such a device has the potential to reduce normal tissue complications for patients undergoing PBS proton therapy.